Question For Cy Willson

I’ve got a question for Cy. I placed it here as I got no response in the steroid forum.

What is initial or distributional half-life, as opposed to terminal half-life? The reason I ask is that someone was asking on another forum if nolva could be taken EOD. I replied that I thought this was fine, as Nolva has a half-life of 5-7 days. Another person then replied that Nolva needs to be taken ED, as the initial or distributional half-life is only 7-14 hours. This person also stated that all protocols call for ED dosages of Nolva, and he knows of no studies confirming the effectiveness of EOD dosages.

So, who’s right here?

Thanks for the help,

Crowbar

[quote]crowbar524 wrote:
I’ve got a question for Cy. I placed it here as I got no response in the steroid forum.

What is initial or distributional half-life, as opposed to terminal half-life? The reason I ask is that someone was asking on another forum if nolva could be taken EOD. I replied that I thought this was fine, as Nolva has a half-life of 5-7 days. Another person then replied that Nolva needs to be taken ED, as the initial or distributional half-life is only 7-14 hours. This person also stated that all protocols call for ED dosages of Nolva, and he knows of no studies confirming the effectiveness of EOD dosages.

So, who’s right here?

Thanks for the help,

Crowbar[/quote]

Sorry, I don’t go on the Steroid portion of the board (for many reasons) and in fact, the Supplements and Nutrition portion is the only part I look over to see if I’m being asked a question.

The distribution half-life is, generally speaking, referring to the phase time in which the drug is going from the blood or richly vascularized organs/tissue to other tissues or end organs which don’t fit that classification. In other words, it’s accounting for the decrease of the drug in the serum, not because the drug is being eliminated but because it’s being distributed to various tissues. This is generally what comprises the first decrease from the initial volume. In short, the drug has not been eliminated, it’s all still in the body, it’s just gone from one portion to another portion of the body.

The elimination half-life on the other hand is when the amount of the drug in the body, period, has been eliminated, approximately by half.

As for who is correct, it really depends on whether you’re talking use as a means of treatment for cancer, or whether you’re talking about a bodybuilder using it, obviously for other reasons. You also have to consider whether the tissue(s) (distribution sites) with highest concentration is the tissue you’re wishing to target in the first place. I will say, however, the statement that this person only knows of using tamoxifen every day when used clinically, is really beside the point as you’re not talking about the drug, any drug, being used clinically when the discussion is taking place on a message board for use with body builders!

So, for determining the use, for example, of Nolva as an anti-estrogen for bodybuilding purposes, do you rely on the terminal half-life or the distributional half-life in determining the optimal doseing schedule–can Nolva be taken EOD and still be an effective anti-estrogen for a bodybuilder?

Thanks,

Crowbar

[quote]crowbar524 wrote:
So, for determining the use, for example, of Nolva as an anti-estrogen for bodybuilding purposes, do you rely on the terminal half-life or the distributional half-life in determining the optimal doseing schedule–can Nolva be taken EOD and still be an effective anti-estrogen for a bodybuilder?

Thanks,

Crowbar [/quote]

Again, it really depends on what you’re talking about, whether it be for increasing LH and endogenous testosterone, gynecomastia, blood lipids, etc.

Anyhow, tamoxifen is kind of an oddball to begin with as the dosage first employed was more of an arbitrary figure than anything else. As a consequence, this is why, if you look in the literature via pubmed, you’ll see at least a few studies evaluating the efficacy of 10 mg every day and 10 mg every other day and comparing it to the standard dosage when used as a prophylaxis in women at a high risk for breast cancer. Interestingly enough, they all, for the most part have concluded that the 10 mg every other day is what could be considered the optimal dosage in terms of both efficacy and safety. This hasn’t been conclusively validated yet, but it makes sense. Anyhow, the data on tamoxifen is focused on use in women, which is again why I fail to see this person’s point of mentioning how it’s used clinically, as the only use in males, and even this is very occasional, is gynecomastia. Talking about what the correct therapeutic levels of a drug should be, which is largely intended for women with or being prone to breast cancer to begin with and applying it to men whom are typically using it for other reasons doesn’t make much sense.

Anyhow, I’m also not clear on what the argument is exactly. If a person is saying that you can’t take 20 mg every other day instead of 10 mg every day, with tamoxifen, I’d have to disagree. Furthermore, the fact is that achieving a steady state with tamoxifen has never been shown to reflect therapeutic efficacy. Also, there are also other ways around it. If one wanted to, they could start with a loading dose and then begin taking smaller amounts every other day.

In the end, the entire reason for trying to find a lower dosage to be used clinically, is because of the potential of serious side effects encountered as the dosages typically employed (deep vein thrombosis and pulmonary embolus could be an issue regardless of sex) and at the same time, never having established a minimally effective dosage.

Anyhow, the elimination half-life is what is typically used to determine a given dosing interval. With tamoxifen the half-life is great enough to where a daily dosing is plenty and in fact, taking it every other day is fine as well for your purposes. This is mainly because there really is no set therapeutic range for this and the pharmacokinetics of tamoxifen spells accumulation over time anyhow. The distribution half-life is really only of use if you’re going to be sampling the blood to try and establish an individual therapeutic regimen. In that type of case, you’re wanting to know when the blood concentration is going to be equal to the tissue concentration and thus you can work to figure out therapeutic dosing according to the response.